PT  - JOURNAL ARTICLE
AU  - WALTER E. MÜLLER
AU  - UWE WOLLERT
TI  - High Stereospecificity of the Benzodiazepine Binding Site on Human Serum Albumin
DP  - 1975 Jan 01
TA  - Molecular Pharmacology
PG  - 52--60
VI  - 11
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/11/1/52.short
4100  - http://molpharm.aspetjournals.org/content/11/1/52.full
SO  - Mol Pharmacol1975 Jan 01; 11
AB  - Using d- and l-oxazepam hemisuccinate (RV 1208 and RV 1210), the stereospecificity of binding of benzodiazepines to human serum albumin was investigated. The interactions of the two enantiomers of oxazepam hemisuccinate with HSA were examined by gel filtration and circular dichroism measurements at pH 7.4 and 8.2. Both enantiomers, RV 1208 and RV 1210, were bound mainly to one binding site at pH 7.4, but there were great differences in the binding constants. Raising the pH to 8.2 decreased the affinity of RV 1208 and increased the affinity of RV 1210. In both enantiomers complex formation with HSA induced similar extrinsic Cotton effects, the signs of which were partly changed by increasing the pH to 8.2. No ligands other than tryptophan exhibit this high degree of stereospecificity of binding to HSA. A theory for the origin of the stereospecific binding is considered. ACKNOWLEDGMENTS The valuable technical assistance of K. Lemmel and B. Lippmann is gratefully acknowledged.